Study Questions:

What is the efficacy of serial low-dose helical computed tomography (CT) screening compared to that of standard single-view posteroanterior (PA) chest radiography (CXR) for early detection of lung cancer?

Methods:

This study was done as part of the National Lung Screening Trial (NLST) comparing CT and CXR for detection of early lung cancer and reduction in lung cancer mortality. Between August 2002 and April 2004, 53,454 persons at high risk for lung cancer were enrolled at 33 US medical centers and randomly assigned to have three annual screenings with either CT or CXR. During follow-up, data were collected for new cases of lung cancer and lung cancer death occurring through December 31, 2009. All CTs were performed on multi-detector scanners with at least four channels and the average radiation exposure was 1.5 mSv per scan. CT scans were considered positive if they revealed any noncalcified nodule measuring ≥4 mm in any diameter. CXRs were classified as positive if revealed any noncalcified nodule or mass “suspicious for lung cancer.” After the third screening, abnormalities suspicious for lung cancer that were stable over the 3-year screening period could be reclassified as a minor abnormality rather than as positive for cancer.

Results:

Over all three rounds, the rate of positive CT scans was 24.2%, 96.4% of which were false positives. The cumulative rate of positive CXR was 6.9%, 94.5% of which were false positives. In the CT group, a total of 1,060 lung cancers were diagnosed (645 per 100,000 person-years) compared to 941 cancers in the CXR group (572 per 100,000 person-years). In the CT group, 649 cancers were diagnosed following a positive CT, 44 after a negative CT, and 367 in subjects who either missed screening or were diagnosed after the screening phase was terminated. In the CXR group, 279 lung cancers were diagnosed after positive CXR, 137 after negative CXR, and 525 in subjects who either missed screening or were diagnosed after the screening phase was completed. In the CT group, 63% of cancers detected after a positive screening test were either stage 1A or 1B, and only 12.8% were stage 4. For cancers detected following a negative screening CT, 15.9% were stage 1A and 1B, and 31.8% were stage 4. For CXR, 43.6% of cancers diagnosed following a positive screening test were stage 1A and 1B, and 20.7% were stage 4, and following a negative screening CXR, diagnosed cancers were stage 1A and 1B in 16.3% and were stage 4 in 44.4% in patients. In the CT group, there were 247 lung cancer deaths per 100,000 person-years compared to 309 per 100,000 person-years in the CXR group, representing relative lung cancer mortality reduction of 20% in the CT group (p = 0.004). All-cause mortality was reduced by 6.7% in the CT group compared to the CXR group (p = 0.02).

Conclusions:

Perspective:

The standard method for lung cancer screening in high-risk patients had been considered routine chest radiography. This study evaluated the utility of multi-detector CT scans configured for low radiation exposure for detection of early lung cancer in high-risk patients and demonstrated an improved ability to detect lung cancer, and furthermore, a reduction in lung cancer mortality, presumably related to earlier detection. Of note, this study was terminated early because of the statistically significant reduction in lung cancer mortality. It should be emphasized that only high-risk patients were enrolled who were 55-74 years of age, and had a ≥30 pack-years smoking history. The groups randomized to CT and CXR were statistically identical with respect to demographics. In view of the known technologic advances of CT scanning compared to a single PA X-ray, the results for early detection are not surprising. This study nicely moved beyond simple detection and demonstrated a clear-cut superiority with respect to preventing lung cancer death. The CT scans used were multi-detector, but have been supplanted by more high-resolution scanners, the use of which may or may not improve upon these results. It should be emphasized in both CT and CXR groups, the majority of positive studies were false positives. Use of even higher resolution multi-detection scanners with 64 or 128 slices potentially could result in an even higher rate of false-positive studies. It should also be emphasized that the NSLT was conducted at medical centers with substantial radiographic experience as well as substantial experience in the diagnosis and treatment of lung cancer, and that these results may not extrapolate to the community. Of this, one of the most important factors in reduction of mortality is the ability to conduct further invasive procedures and/or surgical cure with a low mortality. By way of illustration, the authors note that in the NLST, surgical mortality for lung cancer reduction was 1% compared to 4% in the general population. Also not addressed in the study is the cost-effectiveness of this approach which, as alluded to above, will be heavily dependent upon the rate of false-positive studies and obviously will become a moving target as higher resolution scanners are utilized. At this time, based on this study, it would appear reasonable (cost considerations aside) to consider multi-detector CT scanning at low radiation exposure a viable alternative for lung cancer screening in high-risk patients.